SUMMARY STATEMENT Across mammalian species, appropriate parental behavior is essential for the survival and success of the offspring. In humans, child neglect reportedly occurs in 15?20% of children and can have severe life-long physical and mental consequences. Possibly reflecting the fact that mothers are usually primary caregivers, approximately 70% of perpetrators of child neglect are reported to be the biological mother of the victim. In these cases, the mother?s limited interest, empathy, and interaction with the child can likely be attributed to low maternal motivation. Given that the neural substrates for maternal motivation remain unclear, options to improve maternal motivation are limited. To fill this knowledge gap, we have studied the neural bases of maternal behaviors in a genetically tractable model organism, namely mouse. Using a variety of functional manipulation approaches, we recently found that a genetically defined population of cells in the medial preoptic area (MPOA) is both necessary and sufficient for specific maternal behaviors. Our proposed study will expand on this preliminary finding by seeking to further investigate the natural responses and functions of this population in maternal behaviors. We are particularly interested in addressing whether the population carries information about maternal motivation and whether it mediates flexible pup-seeking behaviors in addition to species-specific innate maternal actions. Answers to these questions are important given that whereas maternal actions differ dramatically across mammalian species, the maternal motivation remains the same. In Aim 1, we will use in vivo recording to examine the natural responses of the cells during various pup-directed behaviors in virgin and lactating females and ask how the responses are influenced by the motivational state of the female towards the pups, which will be determined based on characteristic pup-directed behaviors (e.g. infanticide and pup retrieval). In Aim 2, we will use an operant responding task with pup reinforcement and various functional manipulation tools to address whether the activities of the cells signal the maternal motivation and drive flexible pup-seeking behaviors. This project will not only address a basic question in neuroscience regarding how instinct behavior is generated but also may reveal a key neural population that determines the level of maternal motivation. This knowledge will be essential for developing new strategies to improve maternal motivation and ultimately reduce the incidence of child maltreatment.